VTP-300 / Barinthus Bio - LARVOL DELTA

Off-treatment antiviral efficacy and safety of repeat dosing of imdusiran followed by VTP-300 with or without nivolumab in virally-suppressed, non-cirrhotic subjects with chronic hepatitis B (CHB) (EASL 2025) - "Preliminary off NA treatment follow-up data suggest that repeat dosing of IDR followed by VTP-300 + LDN was well- tolerated and led to HBsAg loss in 3 out of 13 subjects, with 2 approaching functional cure. Additional follow-up data will be presented."

Clinical • Late-breaking abstract • Endocrine Disorders • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Primary analysis of a phase 2b open-label study demonstrates VTP-300 administered with low-dose nivolumab is associated with meaningful reductions of HBsAg in chronic hepatitis B participants with HBsAg less than 200 IU/mL (EASL 2025) - P2 | "VTP-300, a novel antigen-specific investigational immunotherapy, administered in combination with LDN results in meaningful reductions of >1 log in HBsAg at D169 in all 3 treatment groups; all 3 regimens were well tolerated. It is in patients with HBsAg ≤200 IU/mL that HBV directed immunotherapy with the combination of VTP-300 and LDN can achieve HBsAg loss in a meaningful proportion of patients. Further studies investigating sequential therapy of HBsAg lowering agents and VTP-300/LDN in CHB patients are warranted."

Clinical • Late-breaking abstract • P2b data • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Inflammation • Oncology • Solid Tumor • CD8

Data highlighted in late-breaker poster presentation shows that imdusiran achieves functional cure in chronic hepatitis B (cHBV) patients when combined with VTP-300 and low dose nivolumab (GlobeNewswire) - P1b/2a | N=55 | IM-PROVE II (NCT04778904) | Sponsor: Barinthus Biotherapeutics | "All 3 patients had baseline HBsAg <1000 IU/mL. 25% (2/8) of Group C patients with baseline HBsAg <1000 IU/mL who received nivolumab reached functional cure with an overall functional cure rate in Group C of 15.3% (2/13)….Compared to placebo (Group B) more patients treated with imdusiran and VTP-300 (Group A) were able to remain off NA therapy even without achieving functional cure."

P2a data • Hepatitis B

Barinthus Bio Announces Strategic Focus in Immunology and Inflammation (I&I) and Provides a Financial Update (GlobeNewswire) - "Announcement of results from Phase 2b HBV003 clinical trial evaluating additional dosing of VTP-300 and low-dose nivolumab timing in people with chronic hepatitis B infection expected in the second quarter of 2025. Announcement of results from the Phase 2a IM-PROVE II clinical trial evaluating VTP-300, low-dose nivolumab and Arbutus’ imdusiran in people with chronic hepatitis B infection expected in the second quarter of 2025."

P2a data • P2b data • Hepatitis B

Efficacy of VTP-300 in Chronic Hepatitis B Infection (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Barinthus Biotherapeutics | Recruiting ➔ Active, not recruiting | Phase classification: P2b ➔ P2 | Trial completion date: Aug 2024 ➔ Oct 2026 | Trial primary completion date: May 2024 ➔ Feb 2025

Enrollment closed • Phase classification • Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

HBV TARGET SITE FOR THE RNA INTERFERENCE THERAPEUTIC IMDUSIRAN IS HIGHLY CONSERVED IN CHRONIC HEPATITIS B SUBJECTS (AASLD 2024) - "Background: Imdusiran (AB-729, IDR) is an N- Acetylgalactosamine-conjugated small interfering RNA (siRNA) currently being investigated in multiple combination studies, including pegylated interferon-alfa 2a (AB-729-201, IM-PROVE I) and the immunotherapeutic VTP-300 (AB-729-202, IM-PROVE II) for the treatment of chronic hepatitis B (CHB). The IDR target site is highly conserved in baseline samples from CHB subjects enrolled in IDR clinical studies assessed to date. In vitro testing in an HBV cell-based model confirmed retention of IDR activity against tested variants, suggesting that these SNPs have no apparent influence on HBsAg declines in subjects treated with IDR. Imdusiran has demonstrated clinical activity against HBV genotypes A-E."

Clinical • IO biomarker • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Study Investigating the Safety and Immunogenicity of AB-729 and VTP 300 in Virologically Suppressed CHB Participants (ANZCTR) - P2 | N=62 | Active, not recruiting | Sponsor: Arbutus Biopharma | Recruiting ➔ Active, not recruiting | N=40 ➔ 62

Enrollment change • Enrollment closed • Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNG

First-In-Human Study of ChAdOx1-HBV & MVA-HBV Vaccines (VTP-300) for Chronic HBV (clinicaltrials.gov) - P1/2 | N=55 | Completed | Sponsor: Barinthus Biotherapeutics | Active, not recruiting ➔ Completed | Phase classification: P1b/2a ➔ P1/2

Phase classification • Trial completion • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Phase 1b/2a randomized study of heterologous ChAdOx1-HBV/MVA-HBV therapeutic vaccination (VTP-300) as monotherapy and combined with low-dose nivolumab in virally-suppressed patients with chronic hepatitis B. (PubMed, J Hepatol) - "VTP-300 induced CD4+ and CD8+ T cells and lowered HBsAg in a subset of patients with baseline values below 100 IU/ml. The addition of LDN resulted in significant reduction in surface antigen. VTP-300 is a promising immunotherapeutic to move forward alone or in combination therapies."

Journal • Monotherapy • P1/2 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Oncology • CD4 • CD8

Effect of Prior ChAdOx1 COVID-19 Immunisation on T-Cell Responses to ChAdOx1-HBV. (PubMed, Vaccines (Basel)) - "To determine whether prior exposure to ChAdOx1-SARS-CoV2 immunisation (Vaxzevria®) impacts magnitudes of antigen-specific T-cell responses elicited by subsequent administration of the same viral vector (encoding HBV antigens, ChAdOx1-HBV), healthy volunteers that had received Vaxzevria® (n = 15) or the Pfizer or Moderna mRNA COVID-19 vaccine (n = 11) between 10 and 18 weeks prior were recruited to receive a single intramuscular injection of ChAdOx1-HBV. There was no clear correlation between the baseline responses to the adenoviral hexon and the subsequent ELISpot responses. As vaccination within 3 months using the same viral vector backbone affected the insert-specific T-cell responses, a greater interval after prior adenoviral immunisation using heterologous antigens may be warranted in settings in which these cells play critical roles."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Imdusiran (AB-729) administered every 8 weeks for 24 weeks followed by the immunotherapeutic VTP-300 maintains lower HBV surface antigen levels in NA-suppressed CHB subjects than 24 weeks of imdusiran alone (EASL-ILC 2024) - "Study AB-729-202 is an ongoing, randomized, double-blinded Phase 2a study assessing the safety, pharmacodynamics and immunogenicity of repeat doses of imdusiran followed by VTP-300 ± low dose nivolumab or placebo in nucleos(t)ide analogue (NA) suppressed, non-cirrhotic CHB subjects. Repeat dosing of imdusiran for 24 weeks followed by VTP-300 was well-tolerated and contributes to the maintenance of lower HBsAg levels compared to placebo in subjects who have reached EOT and follow up Wk 60. More subjects who received VTP-300 have qualified to stop NA therapy at EOT and all remain off therapy. Additional on-treatment, follow-up and NA discontinuation data including HBV parameters and immunology data will be presented."

Clinical • Hepatitis B

VTP-300 immunotherapeutic, plus low dose PD-1 inhibitor, nivolumab, continues to show meaningful, sustained reductions in HBsAg levels (EASL-ILC 2024) - "Preliminary safety data suggest that VTP-300 in combination with low dose nivolumab has been generally well tolerated and has resulted in meaningful, sustained HBsAg reductions, particularly in participants with baseline HBsAg levels ≤200IU/mL. We believe that VTP-300 is a promising immunotherapeutic candidate for enhancing CHB functional cure rates. VTP-300 is also being investigated in combination with a siRNA inhibitor, imdusiran."

IO biomarker • Endocrine Disorders • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation

PRELIMINARY PHARMACODYNAMICS AND SAFETY OF REPEAT DOSING OF IMDUSIRAN (AB-729) FOLLOWED BY VTP-300 OR PLACEBO IN VIRALLY-SUPPRESSED, NON-CIRRHOTIC SUBJECTS WITH CHRONIC HEPATITIS B (CHB) (AASLD 2023) - "Preliminary data suggest that repeat dosing of imdusiran for 24 weeks followed by VTP-300 was welltolerated and may contribute to prolonged HBsAg reductions compared to placebo. Additional on-treatment and follow-up data including HBV parameters and immunology data will be presented."

Clinical • Late-breaking abstract • PK/PD data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • CD4 • CD8

A PHASE 2b, OPEN-LABEL STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY, IMMUNOGENICITY AND TREATMENT REGIMENS OF VTP-300 COMBINED WITH LOW-DOSE NIVOLUMAB IN CHRONIC HEPATITIS B INFECTION (AASLD 2023) - "VTP-300 is a novel antigen-specific investigational immunotherapy which has shown (in a Phase 1b/2a study) meaningful and durable HBsAg reductions in patients with HBV as a monotherapy and in combination with LDN. Evaluating the addition and timing of PD-1 inhibitor administration and a second boost of MVA-HBV is critical to optimizing the regimen of VTP-300 which may be a critical component of a functional cure regimen."

Clinical • P2b data • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Inflammation • Oncology • Solid Tumor • CD8 • IFNG

HBV001: Phase I study evaluating the safety and immunogenicity of the therapeutic vaccine ChAdOx1-HBV. (PubMed, JHEP Rep) - P1 | "This is an important first step in the development of ChAdOx1-HBV as part of a wider therapeutic strategy to induce hepatitis B functional cure, and is of great interest to patients CHB and clinicians treating the condition. This study is registered at ClinicalTrials.gov (NCT04297917)."

Journal • P1 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Arbutus Announces Pipeline Updates and Dosing of the First Subject in the Phase 1a/1b Clinical Trial with AB-101; Cash Runway Extended (GlobeNewswire) - "The Company remains on track to report preliminary data in the fourth quarter of this year from the Phase 2a clinical trial with imdusiran and Vaccitech’s VTP-300 in patients with cHBV. In addition, the Company has dosed the first subject in its Phase 1a/1b clinical trial with its oral PD-L1 inhibitor, AB-101, for HBV and expects preliminary data in the first half of 2024."

P1 data • P2a data • Trial status • Hepatitis B

Phase 1b/2a study of heterologous ChAdOx1-HBV/MVA-HBV immunotherapy (VTP-300) combined with low-dose nivolumab (LDN) in virally suppressed patients with CHB on nucleos(t)ide analogues (EASL-ILC 2023) - "VTP-300 immunotherapy, as monotherapy and when combined with low dose nivolumab at the boosting time point, was shown during the Phase 1b/2a trial to be immunogenic and associated with sustained reductions in HBsAg levels in well-controlled CHB patients, and was administered with no concerning treatment-related SAEs or safety signal observed."

Clinical • P1/2 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Oncology • CD8

PHASE 1b/2a STUDY OF HETEROLOGOUS ChAdOx1-HBV/MVA-HBV THERAPEUTIC VACCINATION (VTP-300) COMBINED WITH LOW-DOSE NIVOLUMAB (LDN) IN VIRALLYSUPPRESSED PATIENTS WITH CHB ON NUCLEOS(T)IDE ANALOGUES (AASLD 2022) - "VTP-300 immunotherapy, as monotherapy and when combined with low dose nivolumab at the boosting time point, has been immunogenic and shown reduction in HBsAg in well-controlled CHB patients, while exhibiting an excellent safety profile."

Clinical • Late-breaking abstract • P1/2 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • CD8 • IFNG

Efficacy of VTP-300 in Chronic Hepatitis B Infection (clinicaltrials.gov) - P2b | N=120 | Recruiting | Sponsor: Vaccitech (UK) Limited | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatitis B • Hepatology • Infectious Disease • Inflammation

First-In-Human Study of ChAdOx1-HBV & MVA-HBV Vaccines (VTP-300) for Chronic HBV (clinicaltrials.gov) - P1b/2a | N=55 | Active, not recruiting | Sponsor: Vaccitech (UK) Limited | Recruiting ➔ Active, not recruiting | Trial primary completion date: Oct 2022 ➔ Feb 2023

Enrollment closed • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation • CD4 • CD8

First in Human Study of ChAdOx1-HBV (clinicaltrials.gov) - P1 | N=47 | Completed | Sponsor: Vaccitech (UK) Limited | Active, not recruiting ➔ Completed

Monotherapy • Trial completion • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Phase 1b/2a study of heterologous ChAdOx1-HBV/MVA-HBV therapeutic vaccination (VTP-300) combined with low-dose nivolumab (LDN) in virally-suppressed patients with CHB on nucleos(t)ide analogues (EASL-ILC 2022) - "VTP-300 immunotherapy, either alone or combined with nivolumab at the boosting time point, has been immunogenic and shown reduction in SAg in well-controlled CHB patients, while exhibiting an excellent safety profile."

Clinical • P1/2 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • CD8 • IFNG

Efficacy of VTP-300 in Chronic Hepatitis B Infection (clinicaltrials.gov) - P2b | N=120 | Not yet recruiting | Sponsor: Vaccitech (UK) Limited

New P2b trial • Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNG

First in Human Study of ChAdOx1-HBV (clinicaltrials.gov) - P1 | N=47 | Active, not recruiting | Sponsor: Vaccitech (UK) Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Hepatitis B • Hepatology • Infectious Disease • Inflammation

First-In-Human Study of ChAdOx1-HBV & MVA-HBV Vaccines (VTP-300) for Chronic HBV (clinicaltrials.gov) - P1b/2a | N=52 | Recruiting | Sponsor: Vaccitech (UK) Limited | Trial primary completion date: Jun 2022 ➔ Oct 2022

Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation • CD4 • CD8